The delivery of nucleic acids, peptides and other pharmacological agents into animal and plant cells has been an important object of molecular biology and clinical research. A variety of methods are available for delivering nucleic acid artificially into cells. Similar delivery methods are applied to both peptides and other pharmacological agents. The most commonly used methods employ cationic lipids, electroporation and viral transduction and numerous methods that target mechanical or biochemical membrane disruption and/or penetration (e.g., using detergents, microinjection, or particle guns). However, these methods suffer from a variety of disadvantages. For example, while cationic lipids are used most often for DNA and small interfering RNAs (siRNAs) delivery in vitro, they have generally been found to be highly toxic and therefore not appropriate for in vivo delivery applications such as in the treatment of disease. With viral gene delivery, there is a possibility that the replication deficient virus used as a delivery vehicle may revert to wild-type thus becoming pathogenic. Electroporation suffers from poor gene-transfer efficiency and therefore has limited clinical application. Additionally, all of the above delivery methods as applied to patients are not cell or tissue specific resulting in the delivery of nucleic acids, peptides and other pharmacological agents to non-target tissues. This is a highly inefficient means of delivery and subjects a patient's organs and tissues to unneeded metabolic stress.
Alternative methods of delivery included synthetic and biological polypeptides. These delivery methods show great potential as a tool to introduce nucleic acids peptides and other pharmacological agents into cells. However, the repertoire of known polypeptides capable of efficiently delivering pharmacological agents to cells is limited. Moreover, the current state of technology for delivery peptides is still in its infancy and there are no known cell or tissue specific delivery polypeptides.
Thus, there remains a long-standing need in the art for better tools and methods to deliver nucleic acids, peptides and other pharmacological agents into cells, particularly in view of the fact that existing techniques for delivering substances into cells are limited by poor efficiency and/or high toxicity of the delivery reagents. Related needs exist for improved methods and formulations to deliver an effective amount, in an active and enduring state, and using non-toxic delivery vehicles, to selected cells, tissues, or compartments to mediate regulation of gene expression in a manner that will alter a phenotype or disease state of the targeted cells.